Edaravone Ameliorates Diabetes-Induced Dysfunction of NO-Induced Relaxation in Corpus Cavernosum Smooth Muscle in the Rat
Edaravone Ameliorates Diabetes-Induced Dysfunction of NO-Induced Relaxation in Corpus Cavernosum Smooth Muscle in the Rat
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DOI：
10.1111/j.1743-6109.2011.02238.x
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发表时间：
2011-06-01
影响因子：
3.5
通讯作者：
Satoh, Keisuke
中科院分区：
文献类型：
--
作者：
Ohmasa, Fumiya;Saito, Motoaki;Satoh, Keisuke
糖尿病（DM）是勃起功能障碍（艾德）的主要危险因素。虽然糖尿病诱发艾德的病因是多因素的，目前还不清楚，但活性氧被认为是关键因素之一。目的：本文的目的是研究是否给予依达拉奉，一种自由基清除剂，可以防止1型糖尿病诱导的一氧化氮（NO）诱导的大鼠阴茎海绵体平滑肌舒张功能障碍。老年雄性Wistar大鼠随机分为3组。一组用柠檬酸盐-磷酸盐缓冲液加生理盐水处理（组Cont），而在另外两组中，用链脲佐菌素（50 mg/kg腹腔内[i. p.]）诱导糖尿病。随后，用依达拉奉（10 mg/kg/天，i. p.;主要指标：测定血清葡萄糖、丙二醛水平和阴茎环磷酸鸟苷（cGMP）浓度，用去甲肾上腺素介导的收缩和乙酰胆碱介导的舒张来评估阴茎功能。通过实时定量聚合酶链反应（PCR）和免疫印迹分析研究了毒蕈碱M-3受体、神经元型一氧化氮合酶（nNOS）、内皮型NOS（eNOS）和诱导型NOS（iNOS）的参与mRNA水平，以及nNOS、eNOS、磷酸化nNOS和磷酸化eNOS的参与蛋白水平，结果：依达拉奉治疗可部分但显著地预防糖尿病引起的体重和阴茎重量下降。依达拉奉治疗显著改善了糖尿病诱导的丙二醛水平升高、阴茎cGMP浓度降低、糖尿病诱导的去甲肾上腺素介导的收缩增加和乙酰胆碱介导的舒张减少。虽然nNOS中mRNA的表达水平没有显著差异，但糖尿病诱导的M-3受体和iNOS mRNA的上调以及糖尿病诱导的eNOS、磷酸化nNOS、结论：依达拉奉通过改善阴茎海绵体组织中的NO-1，NOS系统，从而部分阻止糖尿病大鼠艾德的发展。Ohmasa F，Saito M，Tsounapi P，Dimitriadis F，Inoue S，Shomori K，Shimizu S，Kinoshita Y，and Satoh K.依达拉奉改善糖尿病大鼠阴茎海绵体平滑肌NO诱导的舒张功能障碍。J Sex Med 2011;8：1638-1649.
Introduction.Diabetes mellitus (DM) represents a major risk factor for erectile dysfunction (ED). Although the etiology of diabetes-induced ED is multifactorial and still unknown, reactive oxygen species are thought to be one of the key factors.Aim.The aim of this article is to investigate whether administration of edaravone, a free radical scavenger, could prevent type 1 diabetes-induced dysfunction of nitric oxide (NO)-induced relaxation in corpus cavernosum smooth muscle in the rat.Methods.Six-week-old male Wistar rats were randomly divided into three groups. One group was treated with citrate-phosphate buffer plus normal saline (group Cont), whereas in the other two groups, diabetes was induced by streptozotocin (50 mg/kg intraperitoneally [i.p.]). Subsequently, the diabetic rats were treated for 4 weeks either with edaravone (10 mg/kg/day, i.p.; group DM + E) or with normal saline (group DM).Main Outcome Measures.Serum glucose and malondialdehyde levels as well as penile cyclic guanosine monophosphate (cGMP) concentrations were determined, and penile function was estimated by organ bath studies with norepinephrine-mediated contractions and acetylcholine-mediated relaxations. The participation mRNA levels of muscarinic M-3 receptors, neuronal nitrous oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS), and participation protein levels of nNOS, eNOS, phosphorylated nNOS, and phosphorylated eNOS were investigated by quantitative real-time polymerase chain reaction (PCR) and immunoblot analysis, respectively.Results.Treatment with edaravone prevented partially but significantly the decreased body and penile weight induced by diabetes. Treatment with edaravone significantly improved the increased diabetes-induced malondialdehyde levels, the decreased penile cGMP concentrations, the increased diabetes-induced norepinephrine-mediated contractions, and the decreased acetylcholine-mediated relaxation. Although there were no significant differences in expression levels of mRNAs in nNOS, diabetes-induced upregulation of muscarinic M-3 receptor and iNOS mRNAs as well as diabetes-induced downregulations of eNOS, phosphorylated nNOS, and phosphorylated eNOS were significantly prevented by edaravone.Conclusions.Edaravone decreases the oxidative insult in the penile corpus cavernosum by ameliorating the NO-NOS system and thus preventing partially the developing ED in DM in the rat. Ohmasa F, Saito M, Tsounapi P, Dimitriadis F, Inoue S, Shomori K, Shimizu S, Kinoshita Y, and Satoh K. Edaravone ameliorates diabetes-induced dysfunction of NO-induced relaxation in corpus cavernosum smooth muscle in the rat. J Sex Med 2011;8:1638-1649.